Multiple sclerosis (MS) is widely-recognized as a neuroinflammatory and neurodegenerative disease [1]. MS lesions are characterized by demyelination, oligodendrocyte death, axonal injury and neuronal loss [2]. Studies have shown that although neural stem cells (NSCs) are abundantly present in MS lesions [3] their differentiation into functional neurons and oligodendrocytes is mostly inconsistent, and many lesions fail to remyelinate successfully [4]. One of the factors known to affect NSCs differentiation is a group of proteins belonging to the transforming growth factor-β (TGFβ) family, named bone morphogenic proteins (BMPs).
Studies have shown that reduced BMP signaling is associated with both neurons [5] and oligodendrocytes [6] development. It has further been demonstrated that during experimental autoimmune encephalomyelitis (EAE), a mouse model for MS, BMPs-4, 6, and 7 are up-regulated in the mouse spinal cord [7]. In addition, PCR analysis of human MS plaques showed that MS lesions express both BMP-4 and BMP-5 mRNA [8].
It has also been demonstrated that BMP family members are expressed in the healthy adult brain, with differing distributions for various family members. Nevertheless, the specific expression profiles of BMP-2, 4, 5 and 7 in the neuroproliferative areas, namely, the subventricular zone (SVZ) and the subgranular zone (SGZ), have been poorly investigated.
U.S. Pat. No. 7,803,752 [9] discloses a method of inducing addition of medium spiny neurons comprising providing a neurotrophic factor and Noggin, an inhibitor of BMP. Specifically, U.S. Pat. No. 7,803,752 concern the treatment of Huntington's disease.